Diisopropylethylamine → Biphenyl-2-ylcarbamic Acid 1-[2-(4-Aminomethylphenylcarbamoyl)ethyl]piperidin-4-yl Ester

HRID 1948181Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1948181
C(OC([NH:8][CH2:9][C:10]1[CH:16]=[CH:15][C:13]([NH2:14])=[CH:12][CH:11]=1)=O)(C)(C)C.[C:17]1([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[NH:23][C:24]([O:26][CH:27]1[CH2:32][CH2:31][N:30]([CH2:33][CH2:34][C:35](O)=[O:36])[CH2:29][CH2:28]1)=[O:25].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.C(O)(C(F)(F)F)=O.C(Cl)Cl>[NH2:8][CH2:9][C:10]1[CH:11]=[CH:12][C:13]([NH:14][C:35]([CH2:34][CH2:33][N:30]2[CH2:29][CH2:28][CH:27]([O:26][C:24](=[O:25])[NH:23][C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=3[C:38]3[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=3)[CH2:32][CH2:31]2)=[O:36])=[CH:15][CH:16]=1

Komponenten

7

Edukt 4

HCID 81531DiisopropylethylamineHCID 2756041tert-butyl N-[(4-aminophenyl)methyl]carbamateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 218806073-[4-(Biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]propionic Acid

Produkt 1

HCID 59340340Biphenyl-2-ylcarbamic Acid 1-[2-(4-Aminomethylphenylcarbamoyl)ethyl]piperidin-4-yl EsterAusbeute 94 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 21863450Trifluoroacetic acid methylene chlorideLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

To a stirred solution of 4-(N-tert-butoxycarbonylaminomethyl)aniline (756 mg, 3.4 mmol), 3-[4-(biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]propionic acid (1.5 g, 4.08 mmol; prepared as described in Preparation 11) and HATU (1.55 g, 4.08 mmol) in DMF (6.8 mL), was added DIPEA (770 μL, 4.42 mmol). The reaction mixture was stirred at 50° C. overnight, and then the solvent was removed under reduced pressure. The resulting residue was dissolved in DCM (20 mL) and washed with saturated aqueous sodium bicarbonate solution (10 mL). The organic phase was then dried over MgSO4 and the solvent was removed under reduced pressure. The crude product was purified by flash chromatography (5-10% MeOH/DCM) to give a solid, which was dissolved in TFA/DCM (25%, 30 mL) and stirred at room temperature for 2 hours. The solvent was then removed under reduced pressure and the crude residue was dissolved in DCM (30 mL) and washed with 1N NaOH (15 mL). The organic phase was separated, dried over MgSO4, filtered and the solvent was removed under reduced pressure to give 1.5 g of the title intermediate (94% yield over 2 steps).

Aufarbeitung

  1. customthe solvent was removed under reduced pressure
  2. dissolutionThe resulting residue was dissolved in DCM (20 mL)
  3. washwashed with saturated aqueous sodium bicarbonate solution (10 mL)
  4. dry with materialThe organic phase was then dried over MgSO4
  5. customthe solvent was removed under reduced pressure
  6. customThe crude product was purified by flash chromatography (5-10% MeOH/DCM)
  7. customto give a solid, which
  8. stirringstirred at room temperature for 2 hours
  9. customThe solvent was then removed under reduced pressure
  10. dissolutionthe crude residue was dissolved in DCM (30 mL)
  11. washwashed with 1N NaOH (15 mL)
  12. customThe organic phase was separated
  13. dry with materialdried over MgSO4
  14. filtrationfiltered
  15. customthe solvent was removed under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-e9d2ebc0e47445629a65bb25fa2b0cf3
Quelldatensatz
uspto-grants-2013_03
Patentnummer
US08399488B2

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